Effects of social isolation and galactic cosmic radiation on fine motor skills and behavioral performance.

Future NASA missions will require astronauts to travel farther and spend longer durations in space than ever before. This will also expose astronauts to longer periods of several physical and psychological challenges, including exposure to space radiation (SR) and periods of social isolation (SI), which could have unknown negative effects on physical and mental health. Each also has the potential to negatively impact sleep which can reduce the ability to cope with stressful experiences and lead to sensorimotor, neurocognitive, and physical deficits. The effects of SI and SR on gross motor performance has been shown to vary, and depend on, individual differences in stress resilience and vulnerability based on our established animal model in which stress produces different effects on sleep. In this study, the impact that SI and SR, either alone or together, had on fine motor skill performance (bilateral tactile adhesive removal task (BTAR)) was assessed in male rats. We also examined emotional, exploratory, and other off-task behavioral responses during testing and assessed whether sensorimotor performance and emotion varied with individual differences in resilience and vulnerability. BTAR task performance was differentially impacted by SI and SR, and were further influenced by the stress resilience/vulnerability phenotype of the rats. These findings further demonstrate that identifying individual responses to stressors that can impact sensorimotor ability and behavior necessary to perform mission-related tasks will be of particular importance for astronauts and future missions. Should similar effects occur in humans, there may be considerable inter-individual variability in the impact that inflight stressors have on astronauts and their ability to perform mission-related tasks.

Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala.

Increasing evidence has connected the development of certain neuropsychiatric disorders, as well as neurodegenerative diseases, to stress-induced dysregulation of the immune system. We have shown that escapable (ES) and inescapable (IS) footshock stress, and memories associated with ES or IS, can differentially alter inflammatory-related gene expression in brain in a region dependent manner. We have also demonstrated that the basolateral amygdala (BLA) regulates stress- and fear memory-induced alterations in sleep, and that differential sleep and immune responses in the brain to ES and IS appear to be integrated during fear conditioning and then reproduced by fear memory recall. In this study, we investigated the role of BLA in influencing regional inflammatory responses within the hippocampus (HPC) and medial prefrontal cortex (mPFC) by optogenetically stimulating or inhibiting BLA in male C57BL/6 mice during footshock stress in our yoked shuttlebox paradigm based on ES and IS. Then, mice were immediately euthanized and RNA extracted from brain regions of interest and loaded into NanoString® Mouse Neuroinflammation Panels for compilation of gene expression profiles. Results showed differential regional effects in gene expression and activated pathways involved in inflammatory-related signaling following ES and IS, and these differences were altered depending on amygdalar excitation or inhibition. These findings demonstrate that the stress-induced immune response, or "parainflammation", is affected by stressor controllability and that BLA influences regional parainflammation to ES or IS in HPC and mPFC. The study illustrates how stress-induced parainflammation can be regulated at the neurocircuit level and suggests that this approach can be useful for uncovering circuit and immune interactions in mediating differential stress outcomes.

Differential Impact of Social Isolation and Space Radiation on Behavior and Motor Learning in Rats.

Future missions to Mars will expose astronauts to several physical and psychological challenges, including exposure to space radiation (SR) and periods of social isolation (SI). Each of these stressors, in addition to mission demands, can affect physical and mental health and potentially negatively impact sleep. The effects of inflight stressors may vary with duration and time course, may be additive or compounding, and may vary with individual differences in stress resilience and vulnerability. Determining how individual differences in resilient and vulnerable phenotypes respond to these mission-related stressors and their interactions with sleep will be crucial for understanding and mitigating factors that can impair performance and damage health. Here, we examined the single and compound effects of ground-based analogs of SI and SR on sensorimotor performance on the balance beam (BB) in rats. We also assessed emotional responses during testing on the BB and assessed whether sensorimotor performance and emotion varied with individual differences in stress resiliency using our established animal model in which stress produces different effects on sleep. Results showed differential motor performance and emotion in the BB task between SI and SR, and these varied based on resilient and vulnerable phenotypes. These findings demonstrate that identifying individual responses to stressors that can impact sensorimotor ability and behavior necessary to perform mission-related tasks will be of particular importance for astronauts and future missions. Should similar effects occur in humans, there may be considerable inter-individual variability in the impact that flight stressors have on the mental health of astronauts and their ability to perform mission-related tasks.

Adiponectin receptors sustain haematopoietic stem cells throughout adulthood by protecting them from inflammation.

How are haematopoietic stem cells (HSCs) protected from inflammation, which increases with age and can deplete HSCs? Adiponectin, an anti-inflammatory factor that is not required for HSC function or haematopoiesis, promotes stem/progenitor cell proliferation after bacterial infection and myeloablation. Adiponectin binds two receptors, AdipoR1 and AdipoR2, which have ceramidase activity that increases upon adiponectin binding. Here we found that adiponectin receptors are non-cell-autonomously required in haematopoietic cells to promote HSC quiescence and self-renewal. Adiponectin receptor signalling suppresses inflammatory cytokine expression by myeloid cells and T cells, including interferon-γ and tumour necrosis factor. Without adiponectin receptors, the levels of these factors increase, chronically activating HSCs, reducing their self-renewal potential and depleting them during ageing. Pathogen infection accelerates this loss of HSC self-renewal potential. Blocking interferon-γ or tumour necrosis factor signalling partially rescues these effects. Adiponectin receptors are thus required in immune cells to sustain HSC quiescence and to prevent premature HSC depletion by reducing inflammation.